Evidence map›Paper›PMID 21653321›Full record

ArticleBlood2011

Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML.

Elspeth M Payne, Niccolò Bolli, Jennifer Rhodes, Omar I Abdel-Wahab, Ross Levine, Cyrus V Hedvat, Richard Stone, Arati Khanna-Gupta, Hong Sun, John P Kanki and 4 more

Abstract read
In one paragraph

Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
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  4. Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025
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  20. Revealing nascent proteomics in signaling pathways and cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 2 countries.

Elspeth M PayneDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. e.payne@ucl.ac.uk
Niccolò Bolli
Jennifer Rhodes
Omar I Abdel-Wahab
Ross Levine
Cyrus V Hedvat
Richard Stone
Arati Khanna-Gupta
Hong Sun
John P Kanki
Hanna T Gazda
Alan H Beggs
Finbarr E Cotter
A Thomas Look
Dana-Farber Cancer Institute · USHarvard University · USMemorial Sloan Kettering Cancer Center · USBrigham and Women's Hospital · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USQueen Mary University of London · GB

Funding

Pathobiology of Cancer at the Host and Population LevelT32CA009382 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI YUAN, ZHI-MIN · 1985 to 2012
$2.9M
Genetic Basis of Myeloid Neoplasia--Mutagenesis ScreensR01CA093152 · NCI · DANA-FARBER CANCER INSTITUTE · PI LOOK, A THOMAS · 2001 to 2005
$2.1M
NCI NIH HHS 5T32 CA009382-26NCI NIH HHS R01 CA093152NCI NIH HHS T32 CA009382
6 · The paper itself

Abstract

In a zebrafish mutagenesis screen to identify genes essential for myelopoiesis, we identified an insertional allele hi1727, which disrupts the gene encoding RNA helicase dead-box 18 (Ddx18). Homozygous Ddx18 mutant embryos exhibit a profound loss of myeloid and erythroid cells along with cardiovascular abnormalities and reduced size. These mutants also display prominent apoptosis and a G1 cell-cycle arrest. Loss of p53, but not Bcl-xl overexpression, rescues myeloid cells to normal levels, suggesting that the hematopoietic defect is because of p53-dependent G1 cell-cycle arrest. We then sequenced primary samples from 262 patients with myeloid malignancies because genes essential for myelopoiesis are often mutated in human leukemias. We identified 4 nonsynonymous sequence variants (NSVs) of DDX18 in acute myeloid leukemia (AML) patient samples. RNA encoding wild-type DDX18 and 3 NSVs rescued the hematopoietic defect, indicating normal DDX18 activity. RNA encoding one mutation, DDX18-E76del, was unable to rescue hematopoiesis, and resulted in reduced myeloid cell numbers in ddx18(hi1727/+) embryos, indicating this NSV likely functions as a dominant-negative allele. These studies demonstrate the use of the zebrafish as a robust in vivo system for assessing the function of genes mutated in AML, which will become increasingly important as more sequence variants are identified by next-generation resequencing technologies.

Indexed as

AllelesAnimalsBlotting, WesternCell CycleCell SeparationDEAD-box RNA HelicasesEmbryo, NonmammalianFlow CytometryHematopoiesisHematopoietic Stem CellsHumansIn Situ HybridizationLeukemia, Myeloid, AcuteMutagenesis, Site-DirectedMutationMyeloid CellsDDX18 protein, humanDdx18 protein, zebrafishDEAD-box RNA HelicasesZebrafish Proteins

Identifiers

PMID21653321
PMCPMC3148170
OpenAlexW2064404284

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.